High dietary phosphate intake in the general population is associated with a higher risk for
developing kidney disease and cardiovascular disease with an increased overall mortality.
Whereas the effects of high phosphate intake on general health become clearer, almost nothing
is known about underlying mechanisms. More recently, the investigators and others found in
animal models that FGF23 stimulates the renal NaCl cotransporter NCC, the target of thiazide
diuretics, and that increased NCC activity may increase blood pressure. The investigators
could also show that increasing dietary phosphate intake in mice, increases FGF23 and NCC
activity within 3 days. Thus, the objective of this single-centre observational cross-over
study including 20-45 year old healthy male probands is to elucidate the role of dietary
phosphate on blood pressure regulation and renal handling of sodium chloride in healthy
subjects. Further the impact of dietary phosphate intake on the regulation of phosphaturic
hormones and other factors regulation blood pressure will be investigated. In addition, the
investigators will examine whether phosphate intake modulates gut microbiome composition. The
primary outcome in this study is the change in blood pressure in healthy subjects on
low-phosphate diet compared to healthy subjects on high-phosphate diet. In addition, to
assess changes in NCC activity as the main mechanism of phosphate-sensitive blood pressure
regulation, renal sodium chloride excretion after administration of hydrochlorothiazide will
be measured. The secondary outcomes of this study are: changes in renal phosphate, calcium
and potassium excretion, changes in phosphate regulation hormones such as 25-OH-Vit. D,
1,25-(OH)2-Vit. D, PTH, FGF23, dopamine in plasma and urine, changes in plasma and urinary
aldosterone levels, changes in sodium/chloride-cotransporter NCC and NaPi-IIa assessed from
urinary exosomes, and changes in stool phosphate excretion and gut microbiome composition.